1. Field of the Invention
This invention pertains generally to implantable devices, and more particularly to an implantable medical device, and surface treatments for the same, for treating diseases and disorders of blood vessels.
2. Description of Related Art
Aneurysms can occur in the neurovasculature. An aneurysm is a spherical out-pouching of blood vessels formed from a localized weakness in the wall of an artery. FIG. 1A illustrates an exemplary cerebral aneurysm 12, which is a localized dilation of the wall of a blood vessel 10. Aneurysms can occasionally rupture and cause a life threatening hemorrhage. Postmortem examinations indicate that 10˜12 million people have brain aneurysms in the United States and 20˜50% will potentially rupture. Aneurysm rupture carries a high rate of morbidity and mortality. Current approaches to prevent aneurysms from rupturing include both surgical and transcatheter methods.
A surgical approach to treat aneurysms by “clipping” the aneurysm neck has been used for a select group of aneurysms. In the open craniotomy or surgical clipping approach shown in FIG. 1B, a surgical clip 16 is used to isolate the aneurysm 14 from the artery 10, and thereby prevent uncontrolled bleeding upon rupture of the aneurysm 14. However, this procedure requires a craniotomy (an opening in the skull) and is not always applicable depending on the aneurysm size, location and complexity.
More recently, transcatheter procedures to treat vascular aneurysms have been developed. In the endovascular coiling or coil embolization approach shown in FIG. 1C, a wire 18 is introduced through the artery 10 and made to coil inside and fill the aneurysm 12. The coiled wire induces formation of a clot in the aneurysm 12, thereby preventing uncontrolled bleeding upon rupture of the aneurysm.
Because the coil embolization technique is less invasive and more cost-effective than surgery, it has become the standard of care for most aneurysms. The coils pack the aneurysm sac 12 densely to limit blood flow in the aneurysm and produce more local thrombosis within the aneurysm.
While coils are beneficial, they can only be used for aneurysms with “necks” narrow enough to hold coils in the aneurysm.
However, certain aneurysms are difficult to treat with the current endovascular coiling or coil embolization approach of FIG. 1C. For example, wide neck aneurysms 20 shown in FIGS. 2A and 2B are dangerous and difficult to treat with endovascular coiling FIG. 2B.
To address this issue, a stent can be placed across the neck of a broad-neck aneurysm and coils placed into the aneurysm through the cells of the stent. This procedure is complicated (it involves two types of devices—a stent and multiple coils) and is limited by the physical size of the stent's delivery system.
The treatment of many disease processes relies on the ability to use a stent that can hold blood vessels open and provides a barrier to the passage of body fluids. Such a stent can also provide a circumferentially occlusive boundary between the stent and the vessel. For example, these stents are useful for re-establishing the integrity of aneurysmal vessels at risk for rupturing. The potential applications of such covered stents are wide-ranging and include the treatment of carotid and coronary artery disease, aortic and central nervous system vascular aneurysms, carotid artery or pulmonary artery stenoses, carotid artery atheromas, and even treatment of ruptured vessels or vessels at risk to rupture.
In the palliation of congenital heart disease, the appropriate stent would be useful for stenting the ductus arteriosus, coarctation of the aorta, or potentially in the treatment of pulmonary artery stenoses and in the stenting of pulmonary veins, an intervention often plagued by in-stent stenosis. Various materials have been used to cover stents, including silicone, polyurethane, and polytetrafluoroethylene. Examples of commercially available covered stents include the polytetrafluoroethylene (PTFE) covered JoStent made by JoMed, the iCAST stent made by Atrium Medical and the CP covered stent that is available from NuMed.
To date, the production of a highly flexible, durable, and thrombus-resistant stent material has not been achieved for all applications. Covered stents generally have a thick covering, making the profile of the stent unacceptably large for certain applications, such as implantation in small and/or tortuous blood vessels, such as found in the vasculature supplying the central nervous system. Accordingly, there are no commercially available covered stents that are low profile enough and flexible enough for use in the neurovasculature.
Thrombotic complications involving indwelling medical devices placed in the vascular are a challenge and burden to patients and our healthcare system as a whole. With the development of new devices as well as concomitant increase in the number of endovascular cases performed, there exists a need to identify ways to limit thrombotic complications associated with vascular devices. The successful treatment of many diseases via endovascular techniques is particularly limited by clot formation on indwelling devices (such as stents). This is especially true in small vessels.
In the 1950s, it was shown that native blood vessels carry a net negative charge. This led to the concept that hydrophilic or electronegative surfaces can provide thromboresistance. When vessel wall injury occurs, the native blood vessel charge at the area of injury turns positive, preferentially attracting negatively charged platelets to the site of injury. While charge is important for thromboresistance, it is not the only factor: surface roughness and binding of other blood products such as fibrinogen or leukocytes have been shown to activate the clotting cascade. Therefore, the ideal covering for indwelling devices would be both hydrophilic and very smooth. Because molecules such as fibrinogen have both hydrophilic and hydrophobic binding sites, both in vitro and in vivo studies are essential in demonstrating that a specific super hydrophilic surface treatment indeed provides a thrombotic advantage to an S-TFN covered stent.
Other surface treatments have been explored for vascular grafts to improve hydrophilicity. These include treatments such as polyethylene glycol and polyethylene oxide which have been shown to prevent platelet adhesion. However, these polymers bond poorly to grafts and have so far been relegated to laboratory science. In the case of ePTFE, the surface is electronegative, but hydrophobic, which has been hypothesized to cause thrombosis in low flow states.
It has been demonstrated that the degree of hydrophilicity, measured by surface wettability, is important in preventing platelet adhesion. While there is evidence that hydrophilic surfaces reduce thrombogenecity, a successful approach that produces a super hydrophilic surface on metals currently used in vascular applications has been absent.
C L. Chu, C Y. Chung, and P K. Chu, “Surface oxidation of NiTi shape memory alloy in a boiling aqueous solution containing hydrogen peroxide,” 2006, Materials Science and Engineering A, 417, pp. 104-109, recently examined that surface treatment of NiTi with 30% H2O2 in a boiling aqueous solution produce approximately 500 nm thick TiO2 eliminating most Ni atoms from the surface in bulk NiTi. This method has been applied to thin film NiTi, but the results did not provide a superhydrophilic surface, and suggest that a superhydrohilic surface was not possible based on their methods. Chu et al. was primarily directed to releasing Ni atoms.
Accordingly, an object of the present invention is a stent having both a low profile and flexibility for use in the neurovasculature.
Another object is a stent having a material and surface treatment for generating a super hydrophilic surface to prevent platelet adhesion. At least some of these objectives will be met in the description below.